Efficacy of Fremanezumab in Migraine Patients with Medication Overuse and Documented Inadequate Response to 2–4 Migraine Preventive Medication Classes: Subgroup Analysis of the Randomized, Placebo-controlled FOCUS Study (4240)

Objective: To evaluate efficacy in a subgroup of patients with baseline medication overuse (use of any acute medication on ≥15 days/month or triptans/ergots/combination medications on ≥10 days/month). Background: The FOCUS study of fremanezumab, a fully-humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), was the first and largest study of a migraine preventive treatment in adults with both chronic migraine (CM) and episodic migraine (EM) and documented inadequate response to 2–4 classes of migraine preventive medications. Design/Methods: Patients were randomized (1:1:1) to quarterly fremanezumab (Month 1: 675mg; Month 2 and 3: placebo), monthly fremanezumab (Month 1: CM, 675mg; EM, 225mg; Months 2 and 3: 225mg), or matched monthly placebo for 12 weeks. Changes from baseline in monthly migraine days and headache days of at least moderate severity at 4 weeks and during 12 weeks of treatment were compared using a mixed-effect model for repeated measures. Results: Of 838 randomized patients, 435 had baseline medication overuse. Reductions from baseline in monthly average migraine days were significantly greater with quarterly fremanezumab (least-squares mean [SE] change, −3.3 [0.61]) and monthly fremanezumab (−4.6 [0.55]) versus placebo (−0.5, [0.62]; both P≤0.0001) during 12 weeks of treatment. Reductions from baseline in monthly average headache days of at least moderate severity were also significantly greater with quarterly fremanezumab (least-squares mean [SE] change, −4.0 [0.61]) and monthly fremanezumab (−5.1 [0.54]) versus placebo (−0.8, [0.61]; both P Conclusions: Quarterly and monthly fremanezumab provided early and sustained reductions in migraine and headache days versus placebo in patients with medication overuse and documented inadequate response to 2–4 classes of migraine preventive medications. Disclosure: Dr. Silberstein has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Abide Therapeutics; Alder Biopharmaceuticals; Allergan, Inc.; Amgen; Avanir Pharmaceuticals, Inc.; Biohaven Pharmaceuticals; Cefaly; Curelator, Inc.; Dr. Reddy’s Laboratories; Egalet Corporation; GlaxoSmithKline Consumer Health Holdings, LLC.; eNeura Inc.; electroCore Medical, LLC; Impel NeuroPharma, Inc.; Lilly USA, LLC; Medscape, LLC; Novartis, Inc.; Satsuma Pharmaceuticals; Supernus Pharmaceuticals, Inc.; Teva Pharmaceuticals; Theranica; and Trigemina, Inc.Dr. Cohen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva%20Pharmaceuticals.Dr. Ramirez Campos has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Teva Pharmaceuticals. Dr. Ramirez Campos has received compensation for serving on the Board of Directors of Teva stocks. Dr. Yang has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Teva Pharmaceuticals Industries. Dr. Galic has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva Pharmaceuticals. Dr. Ning has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Teva Pharmaceuticals Industries. Dr. Jann has nothing to disclose.